70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study

• Published in: Breast cancer research and treatment 2009-07, Vol.116 (2), p.295-302
• Main Authors: Mook, Stella, Schmidt, Marjanka K, Viale, Giuseppe, Pruneri, Giancarlo, Eekhout, Inge, Floore, Arno, Glas, Annuska M, Bogaerts, Jan, Cardoso, Fatima, Piccart-Gebhart, Martine J, Rutgers, Emiel T, van't Veer, Laura J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer research; Cancer therapies; Female; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Hematologic and hematopoietic diseases; Humans; Kaplan-Meier Estimate; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphatic Metastasis - pathology; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local - genetics; Oligonucleotide Array Sequence Analysis; Oncology; Preclinical Study; Prognosis; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-008-0130-2

Purpose The 70-gene prognosis-signature has shown to be a valid prognostic tool in node-negative breast cancer. Although axillary lymph node status is considered to be one of the most important prognostic factors, still 25-30% of node-positive breast cancer patients will remain free of distant metastases, even without adjuvant systemic therapy. We therefore investigated whether the 70-gene prognosis-signature can accurately identify patients with 1-3 positive lymph nodes who have an excellent disease outcome. Methods Frozen tumour samples from 241 patients with operable T1-3 breast cancer, and 1-3 positive axillary lymph nodes, with a median follow-up of 7.8 years, were selected from 2 institutes. Using a customized microarray, tumour samples were analysed for the 70-gene tumour expression signature. In addition, we reanalysed part of a previously described cohort (n = 106) with extended follow-up. Results The 10-year distant metastasis-free (DMFS) and breast cancer specific survival (BCSS) probabilities were 91% (SE 4%) and 96% (SE 2%), respectively for the good prognosis-signature group (99 patients), and 76% (SE 4%) and 76% (SE 4%), respectively for the poor prognosis-signature group (142 patients). The 70-gene signature was significantly superior to the traditional prognostic factors in predicting BCSS with a multivariate hazard ratio (HR) of 7.17 (95% CI 1.81 to 28.43; P = 0.005). Conclusions The 70-gene prognosis-signature outperforms traditional prognostic factors in predicting disease outcome in patients with 1-3 positive nodes. Moreover, the signature can accurately identify patients with an excellent disease outcome in node-positive breast cancer, who may be safely spared adjuvant chemotherapy.